Clinical trial • Phase III • Oncology

ENTRECTINIB for Non-small cell lung cancer (ROS1 gene rearrangement)

Phase III trial of ENTRECTINIB for Non-small cell lung cancer (ROS1 gene rearrangement).

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Non-small cell lung cancer (ROS1 gene rearrangement)
Trial Stage
Phase III
Drug Modality
Small molecule|Small molecule

Key dates

Initial CTIS Submission Date
15-01-2024
First CTIS Authorization Date
16-02-2024

Trial design

Randomised, open-label, crizotinib (xalkori) 200 mg or 250 mg hard capsules, oral (comparator/control arm) Phase III trial in Croatia, Greece, Italy and others.

Randomised
Yes
Open Label
Yes
Comparator
Crizotinib (XALKORI) 200 mg or 250 mg hard capsules, oral (comparator/control arm)
Target Sample Size
115
Trial Duration For Participant
361

Eligibility

Recruits 115 Vulnerable population is selected for this trial (isVulnerablePopulationSelected: true). Specific assent/consent handling text is not provided in the JSON; subject information and informed consent forms (including a "Pregnant Partner" consent form) are listed in the trial documents in multiple languages..

Vulnerable Population
Vulnerable population is selected for this trial (isVulnerablePopulationSelected: true). Specific assent/consent handling text is not provided in the JSON; subject information and informed consent forms (including a "Pregnant Partner" consent form) are listed in the trial documents in multiple languages.

Inclusion criteria

  • {"criterion_text":"- Histologically or cytologically-confirmed diagnosis of advanced or recurrent (Stage IIIB/C not amenable for radical treatment) or metastatic (Stage IV) NSCLC that harbors a documented ROS1 gene rearrangement\n- No prior treatment with a ROS1 tyrosine kinase inhibitor, chemotherapy or other systemic therapy for advanced or recurrent (Stage IIIB/C not amenable for radical treatment) or metastatic (Stage IV) NSCLC\n- Prior radiotherapy is allowed if more than 14 days have elapsed between the end of treatment and randomization\n- Measurable systemic disease according to RECIST v1.1\n- Participants with measurable and non-measurable CNS lesions per RECIST v1.1, including leptomeningeal carcinomatosis\n- Life expectancy of at least 12 weeks"}

Exclusion criteria

  • {"criterion_text":"- Prior treatment with a ROS1 tyrosine kinase inhibitor, chemotherapy or other systemic therapy for advanced or recurrent (Stage IIIB/C not amenable for radical treatment) or metastatic (Stage IV) NSCLC\n- NCI-CTCAE v5.0 Grade 3 or higher toxicities due to any prior therapy (excluding alopecia, fatigue, nausea and lack of appetite), which have not shown improvement and are strictly considered to interfere with current study drug\n- History of recent (within the past 3 months) symptomatic congestive heart failure or ejection fraction ≤ 50% observed during screening for the study\n- History of prolonged corrected QTc interval\n- Peripheral sensory neuropathy ≥ Grade 2\n- Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 1. Progression-free survival (PFS) in patients with CNS metastases at baseline, defined as the time from randomization to the first documented disease progression (extracranial or intracranial) or death from any cause, whichever occurs first, as determined by a blinded independent review committee (BIRC) using RECIST v1.1","definition_or_measurement_approach":"Defined as time from randomization to first documented disease progression (extracranial or intracranial) or death, whichever occurs first; assessed by a blinded independent review committee (BIRC) using RECIST v1.1."}

Secondary endpoints

  • {"endpoint_text":"- 1. Progression-free survival in the CNS (CNS-PFS), defined as the time from randomization to the first documented disease progression in the CNS or death from any cause, whichever occurs first, as determined by the BIRC using RECIST v1.1","definition_or_measurement_approach":"Time from randomization to first documented CNS progression or death; assessed by BIRC using RECIST v1.1."}
  • {"endpoint_text":"- 2. Overall response rate (ORR), defined as the percentage of patients who attain CR or PR, as assessed by the BIRC and the investigator per RECIST v1.1","definition_or_measurement_approach":"Percentage of patients with complete response (CR) or partial response (PR) per RECIST v1.1; assessed by BIRC and investigator."}
  • {"endpoint_text":"- 3. Duration of response (DOR), defined as the time from when response (CR or PR) is first documented to disease progression or death, whichever occurs first, as assessed by the BIRC and the investigator per RECIST v1.1","definition_or_measurement_approach":"Time from first documented CR/PR to disease progression or death; assessed by BIRC and investigator using RECIST v1.1."}
  • {"endpoint_text":"- 4. Progression-free survival (PFS), defined as the time from randomization to the first documented disease progression (extracranial or intracranial) or death from any cause, whichever occurs first, as determined by the BICR and investigator using RECIST v1.1","definition_or_measurement_approach":"Time from randomization to first documented extracranial or intracranial progression or death; assessed by BICR and investigator per RECIST v1.1."}
  • {"endpoint_text":"- 5. Overall survival (OS), defined as the time from randomization to death from any cause","definition_or_measurement_approach":"Time from randomization to death from any cause."}
  • {"endpoint_text":"- 6. Impact on functioning, including health-related quality of life, using the Global Health Status/Quality of Life (GHS/QoL), the Physical Functioning (PF) and Role Function (RF) scores, as assessed by the EORTC QLQ-C30 and analyzed as a time to first and confirmed clinically meaningful deterioration","definition_or_measurement_approach":"Health-related quality of life assessed with EORTC QLQ-C30 (GHS/QoL, PF, RF); analyzed as time to first confirmed clinically meaningful deterioration."}
  • {"endpoint_text":"- 7. Impact on lung cancer-specific symptoms, as assessed by the EORTC QLQ-LC13","definition_or_measurement_approach":"Lung cancer-specific symptom assessment using EORTC QLQ-LC13."}
  • {"endpoint_text":"- 8. Objective response rate in the CNS (CNS-ORR), defined as the percentage of patients who attain CR or PR for lesions in the CNS, as determined by the BICR per RECIST v1.1","definition_or_measurement_approach":"Percentage of patients achieving CR or PR for CNS lesions per RECIST v1.1 as determined by BICR."}
  • {"endpoint_text":"- 9. Duration of response in the CNS (CNS-DOR), defined as the time from when a CNS response (CR or PR) is first documented to disease progression in the CNS, as determined by the BICR per RECIST v1.1","definition_or_measurement_approach":"Time from first documented CNS CR/PR to CNS disease progression; determined by BICR per RECIST v1.1."}
  • {"endpoint_text":"- 10. Incidence, type, timing, relatedness and severity of adverse events , including serious adverse events and adverse events leading to dose modifications/interruptions, study drug withdrawal or death, as assessed by the investigator according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0","definition_or_measurement_approach":"Assessment of adverse events (incidence, type, timing, relatedness, severity), including SAEs and events leading to dose changes or withdrawal; graded per NCI CTCAE v5.0 by investigator."}
  • {"endpoint_text":"- 11. Health utility from the EQ-5D-5L and pharmacoeconomic model","definition_or_measurement_approach":"Health utility measured using EQ-5D-5L for pharmacoeconomic modelling."}

Recruitment

Planned Sample Size
115
Recruitment Window Months
71
Consent Approach
Informed consent obtained using subject information and informed consent forms; multiple ICF/SIS documents are listed in the trial documents in multiple languages (English, German, French, Spanish, Italian, Dutch, Greek, Croatian, Romanian, Swedish, Slovak, etc.). A "Pregnant Partner" consent form is listed. Specific text describing assent or age-specific consent procedures is not provided in the JSON.

Geography

Total Number Of Sites
43
Total Number Of Participants
91

Croatia

Earliest CTIS Part Ii Submission Date
29-01-2024
Latest Decision Or Authorization Date
20-02-2024
Processing Time Days
22
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
KBC Zagreb
Department Name
Department of Pulmonary Diseases
Contact Person Name
Miroslav Samarzija
Contact Person Email
predstojnik.kpb@kbc-zagreb.hr

Greece

Earliest CTIS Part Ii Submission Date
29-01-2024
Latest Decision Or Authorization Date
29-03-2024
Processing Time Days
60
Number Of Sites
4
Number Of Participants
5

Sites

Site Name
Euromedica General Clinic Of Thessaloniki
Department Name
Oncology Department
Contact Person Name
George Fountzilas
Contact Person Email
sofialampaki@yahoo.gr
Site Name
General University Hospital Of Larissa
Department Name
Medical Oncology
Contact Person Name
Athanasios Kotsakis
Contact Person Email
tsoflikigeorgia@gmail.com
Site Name
Thoracic General Hospital Of Athens I Sotiria
Department Name
3rd Dept. of Internal Medicine, Oncology Unit
Contact Person Name
Konstantinos Syrigos
Contact Person Email
ksyrigos.trials@gmail.com
Site Name
Metropolitan Hospital
Department Name
4th Oncology department
Contact Person Name
Helena Linardou
Contact Person Email
elinardou@otenet.gr

Italy

Earliest CTIS Part Ii Submission Date
29-01-2024
Latest Decision Or Authorization Date
27-03-2024
Processing Time Days
58
Number Of Sites
9
Number Of Participants
14

Sites

Site Name
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Department Name
Oncologia Clinica Sperimentale Toraco-Polmonare
Contact Person Name
Alessandro Morabito
Site Name
Istituto Oncologico Veneto
Department Name
Oncologia Medica 2
Contact Person Name
Laura Bonanno
Contact Person Email
laura.bonanno@iov.veneto.it
Site Name
Fondazione IRCCS San Gerardo Dei Tintori
Department Name
S.C. Oncologia Medica S.S. Lung Unit
Contact Person Name
Diego Cortinovis
Site Name
ASST Grande Ospedale Metropolitano Niguarda
Department Name
Dipartimento Di Ematologia Ed Oncologia
Contact Person Name
Salvatore Siena
Site Name
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
Department Name
Dipartimento di Oncologia
Contact Person Name
Silvia Novello
Contact Person Email
silvia.novello@unito.it
Site Name
Azienda Ospedaliero Universitaria Pisana
Department Name
UP Pneumologia
Contact Person Name
Antonio Chella
Contact Person Email
a.chella@ao-pisa.toscana.it
Site Name
IRCCS Ospedale Policlinico San Martino
Department Name
Clinica di Oncologia Medica
Contact Person Name
Carlo Genova
Contact Person Email
carlo.genova@hsanmartino.it
Site Name
I.F.O. Istituti Fisioterapici Ospitalieri
Department Name
Oncologia Medica B
Contact Person Name
Lorenza Landi
Contact Person Email
lorenza.landi@ifo.it
Site Name
San Camillo Forlanini Hospital
Department Name
U.O.C. Pneumologia Ad Indirizzo Oncologico 1
Contact Person Name
Serena Ricciardi

Romania

Earliest CTIS Part Ii Submission Date
29-01-2024
Latest Decision Or Authorization Date
21-02-2024
Processing Time Days
23
Number Of Sites
6
Number Of Participants
8

Sites

Site Name
Centrul De Oncologie SF Nectarie S.R.L.
Department Name
Oncology
Contact Person Name
Michael Schenker
Contact Person Email
office@centruldeoncologie.ro
Site Name
Institute Of Oncology Prof. Dr. Ion Chiricuta Cluj-Napoca
Department Name
Oncology
Contact Person Name
Tudor Ciuleanu
Contact Person Email
office@iocn.ro
Site Name
Spitalul Municipal Ploiesti
Department Name
Oncology
Contact Person Name
Amedeia Nita
Contact Person Email
spitalschuller@yahoo.com
Site Name
Oncomed S.R.L.
Department Name
Oncology
Contact Person Name
Dorel Popovici
Contact Person Email
cabinet_oncomed@yahoo.com
Site Name
Institutul Regional De Oncologie Iasi
Department Name
Oncology
Contact Person Name
Mihai Marinca
Contact Person Email
oncoiasi@iroiasi.ro
Site Name
Radiotherapy Center Cluj S.R.L.
Department Name
Oncology
Contact Person Name
Andrei Ungureanu

Spain

Earliest CTIS Part Ii Submission Date
29-01-2024
Latest Decision Or Authorization Date
16-02-2024
Processing Time Days
18
Number Of Sites
5
Number Of Participants
16

Sites

Site Name
Complexo Hospitalario Universitario A Coruna
Department Name
Oncology
Contact Person Name
M. Rosario Garcia Campelo
Site Name
Institut Catala D'oncologia
Department Name
Oncology
Contact Person Name
Ernest Nadal
Contact Person Email
esnadal@iconcologia.net
Site Name
Hospital Universitario Regional De Malaga
Department Name
Oncology
Contact Person Name
Manuel Cobo-Dols
Contact Person Email
manuelcobodols@yahoo.es
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Oncology
Contact Person Name
Pilar Garrido Lopez
Contact Person Email
pilargarridol@gmail.com
Site Name
Hospital Del Mar
Department Name
Oncology
Contact Person Name
Edurne Arriola Aperribay
Contact Person Email
earriola@psmar.cat

Slovakia

Earliest CTIS Part Ii Submission Date
29-01-2024
Latest Decision Or Authorization Date
16-02-2024
Processing Time Days
18
Number Of Sites
2
Number Of Participants
5

Sites

Site Name
Vychodoslovensky Onkologicky Ustav a.s.
Department Name
Oddelenie klinickej onkolgie
Contact Person Name
Igor Andrasina
Contact Person Email
andrasina@vou.sk
Site Name
University Hospital Bratislava
Department Name
Klinika pneumologie, ftizeologie a funkcnej diagnostiky SZU a UNB
Contact Person Name
Zuzana Svihelova Liskova
Contact Person Email
zuzana.svihel@gmail.com

Germany

Earliest CTIS Part Ii Submission Date
29-01-2024
Latest Decision Or Authorization Date
27-02-2024
Processing Time Days
29
Number Of Sites
5
Number Of Participants
10

Sites

Site Name
Kliniken Maria Hilf GmbH Moenchengladbach
Department Name
Kliniken Maria Hilf GmbH, Krankenhaus St. Franziskus
Contact Person Name
Ullrich Graeven
Contact Person Email
ullrich.graeven@mariahilf.de
Site Name
Pius-Hospital Oldenburg
Department Name
Haematologie und Onkologie
Contact Person Name
Frank Griesinger
Contact Person Email
onkologie@pius-hospital.de
Site Name
HELIOS Klinikum Emil von Behring GmbH
Department Name
Pneumologie Onkologie u.Infektiologie
Contact Person Name
Daniel Misch
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Universitätsklinikum Hamburg-Eppendorf; Med. II. Klinik
Contact Person Name
Maximilian Christopeit
Contact Person Email
m.christopeit@uke.de
Site Name
Justus-Liebig-Universitaet Giessen
Department Name
Universitaetsklinikum Giessen und Marburg GmbH; Medizinische Klinik IV und V
Contact Person Name
Thomas Wehler

Netherlands

Earliest CTIS Part Ii Submission Date
29-01-2024
Latest Decision Or Authorization Date
16-02-2024
Processing Time Days
18
Number Of Sites
3
Number Of Participants
12

Sites

Site Name
Radboud universitair medisch centrum / RADBOUDUMC
Department Name
Lung Oncology
Contact Person Name
Miep van der Drift
Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Long Oncology
Contact Person Name
Annemarie Dingemans
Site Name
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
Department Name
Long Oncologie
Contact Person Name
Joop de Langen
Contact Person Email
j.d.langen@nki.nl

France

Earliest CTIS Part Ii Submission Date
29-01-2024
Latest Decision Or Authorization Date
21-02-2024
Processing Time Days
23
Number Of Sites
7
Number Of Participants
14

Sites

Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Cancérologie-pneumologie
Contact Person Name
Audrey RABEAU
Contact Person Email
rabeau.a@chu-toulouse.fr
Site Name
Assistance Publique Hopitaux De Marseille
Department Name
Cancérologie-pneumologie
Contact Person Name
Pascale TOMASINI
Contact Person Email
pascale.tomasini@ap-hm.fr
Site Name
Institut Bergonie
Department Name
Cancérologie-pneumologie
Contact Person Name
Sophie COUSIN
Contact Person Email
s.cousin@bordeaux.unicancer.fr
Site Name
Hopitaux Prives De Metz
Department Name
Cancérologie-pneumologie
Contact Person Name
Lucile ROUSSEL
Contact Person Email
lucile.roussel@uneos.fr
Site Name
Centre Leon Berard
Department Name
Cancérologie-pneumologie
Contact Person Name
Maurice PEROL
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Cancérologie-pneumologie
Contact Person Name
Alexis CORTOT
Contact Person Email
alexis.cortot@chru-lille.fr
Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
Cancérologie-pneumologie
Contact Person Name
Herve LENA
Contact Person Email
herve.lena@chu-rennes.fr

Sweden

Earliest CTIS Part Ii Submission Date
29-01-2024
Latest Decision Or Authorization Date
16-02-2024
Processing Time Days
18
Number Of Sites
1
Number Of Participants
4

Sites

Site Name
Karolinska University Hospital
Department Name
Tema Cancer, Huvud-, Hals-, Lung- och Hudcancer
Contact Person Name
Karam Al Jirf

Sponsor

Primary sponsor

Full Name
F. Hoffmann-La Roche AG
Organisation Type
Pharmaceutical company
Country Of Registered Address
Switzerland

Contract research organisations

Name
IQVIA Limited
Responsibilities
Monitoring
Name
PPD Development LP
Responsibilities
code 5
Name
Bioclinica Inc.
Responsibilities
Other Third Party Duty
Name
Cytel Inc.
Responsibilities
code 10

Third parties

  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"Speciality Laboratory","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Monitoring","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Other Third Party Duty","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Cytel Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Almac","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"Speciality Laboratory","organisation_type":"Laboratory/Research/Testing facility"}

Investigational products

Investigational Product Name
Rozlytrek 100 mg / Rozlytrek 200 mg hard capsules (entrectinib)
Active Substance
ENTRECTINIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
Oral
Authorisation Status
Marketing authorised (has marketing authorisation number for some presentations)
Starting Dose
Rozlytrek 100 mg or 200 mg hard capsules (oral) (presentations listed)
Dose Levels
100 mg, 200 mg (hard capsules presentations listed)
Maximum Dose
600 mg (maxDailyDoseAmount listed)
Investigational Product Name
XALKORI 200 mg / XALKORI 250 mg hard capsules (crizotinib)
Active Substance
CRIZOTINIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
Oral
Authorisation Status
Marketing authorised (has marketing authorisation number)
Starting Dose
XALKORI 200 mg or 250 mg hard capsules (oral) (presentations listed)
Dose Levels
200 mg, 250 mg (hard capsules presentations listed)
Maximum Dose
500 mg (maxDailyDoseAmount listed)

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